The studies proposed here are designed to elucidate the molecular bases for the intrinsic modulation(s) of the activities of a pyrimidine recycling enzyme, TdR kinase, or its isoenzymes and to evaluate the physiological significance of such regulatory change(s) and potential interactions with closely associated enzymes in the maintenance of intracellular deoxythymidylate pools in diverse human tissues. Comparative studies of TdR kinase and TdR phosphorylase activities will be carried out in 1) a wide spectrum of normal proliferating, differentiated and malignant tissues, 2) fibroblasts from normal subjects and individuals at high risk (hereditary as well as non-hereditary), and 3) normal and malignant cells in culture. These studies should provide adequate background and the proper perspectives for evaluating the regulation of TdR kinase and its overall metabolic role. Enzymes will be characterized by standard biochemical and physicochemical parameters as well as by their antigenic properties. The latter, in conjunction with studies assessing the contribution by various intracellular metabolites to aggregation-disaggregation of kinases in colon, placenta and tumors, can lend insight into regulation during both normal and aberrant proliferation. Antigenicity and biochemical properties will be assessed along with kinase-like and phosphorylase activities in human plasma for potential diagnostic value in the detection of premalignant changes, recurrence of malignancy during and after treatment as well as responses in the course of therapy.